Novel DNA Topoisomerase IIα Inhibitors from Combined Ligand- and Structure-Based Virtual Screening
Figure 4
Topoisomerase 2α-mediated DNA cleavage by mitonafide, etoposide and in silico selected compounds.
Structures of tested compounds and controls are shown on the right. A) Compounds were tested on a portion of SV40 sequence at three different concentrations (100, 10 and 1 µM). The first lane represents the DNA without enzyme and the second lane the DNA with enzyme in presence of DMSO (drug solvent). B) Same as in (A) but compounds were tested on pBR322 plasmid DNA at 100 µM concentration. C) The four active inhibitors of Top2α identified in (B) were additionally tested at 100, 10 and 1 µM concentration on pBR322 substrate.